Virology
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Robert E. Kingston, Ph.D.

Professor of Genetics

Massachusetts General Hospital
Wellman 10
50 Blossom Street
Boston, MA 02114

Tel: 617-726-5990
Fax: 617-726-5949
e-mail:kingston@frodo.mgh.harvard.edu
6 postdoctoral fellows, 6 graduate students

 

We work on the mechanisms that allow a gene to faithfully "remember" whether it should be on or off throughout the lifetime of an organism. Many master regulatory factors, such as the products of Homeobox (Hox) genes, must be expressed in cells in one portion of the body, and be kept silent in other portions of the body. The expression pattern of Hox genes is established early in embryonic development in an appropriate pattern, and the products of Hox genes help specify body pattern. During early embrogenesis Hox patterns are established by the action of factors that are only transiently expressed. These embryonic patterns are maintained throughout the lifetime of the organism by a different group of proteins that are encoded by the Polycomb-Group (PcG) and Thrithorax-Group (trxG) genes. We study the action of protein complexes in the PcG and trxG families.

Complexes in the trxG and PcG families regulate chromatin structure to maintain an active state (trxG) or a repressed state (PcG). We study ATP-dependent nucleosome remodeling complexes encoded by the trxG genes. These complexes use the energy of ATP hydrolysis to alter nucleosome structure in a manner that makes nucleosomal DNA accessible to DNA binding factors. We analyze the mechanisms by which this occurs and the nature of the remodeled products. We also study PcG complexes. These complexes repress transcription by creating a chromatin structure that specifically excludes proteins needed for the transcription process. We are characterizing the mechanisms of action of these complexes, the mechanisms that target these complexes to specific genes, and the mechanisms that allow these complexes to maintain association with the template across cell division and therefore faithfully remember the expression state of the gene. We have initiated studies on the overall chromatin organization of the mammalian Hox clusters so that we can integrate these mechanistic studies with regulatory events that occur as mammals develop.

 

References:

  1. Francis, N.J., Saurin, A.J., Shao, Z. and R.E. Kingston (2001) Reconstitution of a functional core polycomb repressive complex. Mol. Cell 8:545-556.
  2. Narlikar, G.F., Phelan, M. and R.E. Kingston (2001) Generation and interconversion of multiple distinct nucleosomal states as a mechanism for catalyzing chromatin fluidity. Mol Cell. 8:1219-1230.
  3. Francis, N.J. and R.E. Kingston (2001). Mechanisms of transcriptional memory. Nature Reviews, Mol. Cell. Biol. 2: 409-421.
  4. Narlikar, G.J., Fan, H-Y., and R.E. Kingston (2002). Cooperation between complexes that regulate